血管扩张器反应性肺动脉高血压的周围血液特征
Anna R Hemnes1, Aaron W Trammell2, Stephen L Archer2
1From the Division of Allergy, Pulmonary, and Critical Care Medicine (A.R.H., A.W.T., N.P., M.F., L.W., I.M.R., J.H.N., J.W.) and Department of Biostatistics (C.Y., H.N.), Vanderbilt University School of Medicine, Nashville, TN; Department of Medicine, Queen's University, Kingston, Ontario, Canada (S.L.A.); Division of Cardiology, University of Chicago, Chicago, IL (S.R.); and Division of Allergy, Immunology, and Pulmonary Medicine, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN (E.D.A.). anna.r.hemnes@vanderbilt.edu.
肺动脉高血压 (PAH) 患者的反应各不相同. 研究人员在外周血液中确定了不同的RNA表达模式,以区分血管扩张器反应的PAH (VR-PAH) 和血管扩张器不反应的PAH (VN-PAH),帮助选择治疗.
科学领域:
- 心血管研究研究心血管研究
- 分子生物学分子生物学
- 基因组学就是基因组学.
背景情况:
- 肺动脉高血压 (PAH) 在治疗反应中表现出显著的异质性.
- 与血管扩散剂不响应的PAH (VN-PAH) 相比,血管扩散剂响应的PAH (VR-PAH) 患者表现得更好,并且对通道阻塞剂有更好的反应.
- VR-PAH和VN-PAH之间潜在的分子差异尚未完全理解,但可能在周围血液中检测到.
研究的目的:
- 调查VR-PAH和VN-PAH之间是否存在不同的分子原因.
- 确定能够区分VR-PAH和VN-PAH表型的外周血液生物标志物.
- 探索这些生物标志物的潜力,以预测有利的治疗反应.
主要方法:
- 从VR-PAH和VN-PAH患者的培养淋巴细胞上使用微阵列的基因表达概况.
- 在外围血液上进行定量聚合酶链反应 (qPCR),以分析顶部不同基因的表达.
- 使用基因表达数据对VR-PAH患者进行分类的决策树模型的开发和验证.
主要成果:
- 微阵列分析显示了VR-PAH和VN-PAH之间基因表达模式的显著差异,特别是涉及细胞-细胞粘附,细胞骨和rho-GTPase基因.
- 在全血中测试的25个基因中,有13个基因表现出显著的差异性表达,包括EPDR1,DSG2和RHOQ.
- 主要使用DSG2和RHOQ表达水平的决策树模型,在验证队列中准确识别了100%的VR-PAH患者.
结论:
- 周围血液中的RNA表达模式可以有效地区分VR-PAH和VN-PAH.
- 这些独特的分子特征表明这两种PAH表型的潜在原因不同.
- 开发的生物标志物方法有望用于识别可能对特定治疗有好反应的PAH患者.
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